Vertebrate TFPI-2 C-terminal peptides exert therapeutic applications against Gram-negative infections

BMC Microbiology

Research Article

Praveen Papareddy¹  Emanuel Smeds¹  Louise Wrange¹  Emelie Holmberg¹  Gopinath Kasetty²  Selvi Adikesavan³ 

[1] Division of Infection Medicine, Department of Clinical Sciences, Lund University, Biomedical Center, B14, Tornavägen 10, SE-221 84, Lund, Sweden;Division of Respiratory Medicine and Allergology, Lund University, Lund, Sweden;School of Biosciences and Technology, Environmental Division, VIT University, Tamil Nadu, India;Dept of Biotechnology, DKM college for Women, Sainathapuram, 632001, Vellore, India;

关键词: TFPI-2;    Peptide;    Complement;    Vertebrates;    Antimicrobial;    Coagulation;    Sepsis;    Evolution;   

DOI  :  10.1186/s12866-016-0750-3

 received in 2016-01-08, accepted in 2016-06-15,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundTissue factor pathway inhibitor-2 (TFPI-2) is a serine protease inhibitor that exerts multiple physiological and patho-physiological activities involving the modulation of coagulation, angiogenesis, tumor invasion, and apoptosis. In previous studies we reported a novel role of human TFPI-2 in innate immunity by serving as a precursor for host defense peptides. Here we employed a number of TFPI-2 derived peptides from different vertebrate species and found that their antibacterial activity is evolutionary conserved although the amino acid sequence is not well conserved. We further studied the theraputic potential of one selected TFPI-2 derived peptide (mouse) in a murine sepsis model.ResultsHydrophobicity and net charge of many peptides play a important role in their host defence to invading bacterial pathogens. In vertebrates, the C-terminal portion of TFPI-2 consists of a highly conserved cluster of positively charged amino acids which may point to an antimicrobial activity. Thus a number of selected C-terminal TFPI-2 derived peptides from different species were synthesized and it was found that all of them exert antimicrobial activity against E. coli and P. aeruginosa. The peptide-mediated killing of E. coli was enhanced in human plasma, suggesting an involvement of the classical pathway of the complement. Under in vitro conditions the peptides displayed anti-coagulant activity by modulating the intrinsic pathway of coagulation and in vivo treatment with the mouse derived VKG24 peptide protects mice from an otherwise lethal LPS shock model.ConclusionsOur results suggest that the evolutionary conserved C-terminal part of TFPI-2 is an interesting agent for the development of novel antimicrobial therapies.

【 授权许可】

CC BY   
© The Author(s). 2016